scholarly journals Plasmodium falciparum schizont stage transcriptome variation among clinical isolates and laboratory-adapted clones

2018 ◽  
Author(s):  
Sarah J Tarr ◽  
Ofelia Díaz-Ingelmo ◽  
Lindsay B Stewart ◽  
Suzanne E Hocking ◽  
Lee Murray ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Differentially Expressed ◽  
Clinical Isolates ◽  
Schizont Stage ◽  
Variable Expression ◽  
The Impact

AbstractMalaria parasite genes exhibit variation in both sequence and expression level. There is much information on sequence polymorphism, but less resolution on natural variation in transcriptomes of parasites at specific developmental stages. This is largely because it is challenging to obtain highly replicated sampling of transcriptomes to overcome potentially confounding technical and biological variation. We address the issue in the major human parasite Plasmodium falciparum by obtaining RNA-seq profiles of multiple independent replicate preparations of mature schizont-stage parasites from a panel of clinical isolates recently established in culture and from long-term laboratory-adapted clones. With a goal of robustly identifying variably expressed genes, we show that increasing the numbers of biological sample replicates greatly improves the discovery rate. Generally, six independent replicates of each parasite culture is recommendable as being significantly to lower numbers, although for highly expressed genes variable expression can be detected when fewer replicates are available. A broad comparison identifies genes differing in relative expression between cultured clinical isolates and laboratory-adapted clones. Genes more highly expressed in the laboratory-adapted clones include an AP2 transcription factor gene Pf3D7_0420300 and putative methyl transferase genes. The variable expression of several known merozoite invasion ligands is confirmed, and previously uncharacterised genes are shown to be differentially expressed among clinical isolates. New RT-qPCR assays validate the variation in transcript levels of these genes, and allow quantitation of expression to be extended to a wider panel of clinical isolate samples. These variably expressed genes are new candidates for investigation as potential determinants of alternative parasite developmental pathways or targets of immunity.Author summaryUnderstanding parasite diversity and adaptation may require characterisation of gene expression variation, and is vital if chemotherapeutic or vaccine development is to consider new candidate targets, but it is technically challenging to generate precise data on clinical isolates. Here, we analyse the transcriptomes of mature Plasmodium falciparum schizonts using RNA-sequencing, using large numbers of biological replicate samples to minimise the impact of inter-replicate variation on observed patterns of differential expression. This identifies genes that are differentially expressed in long term laboratory-adapted parasites and recently cultured clinical isolates, as well as among different clinical isolates. In additional samples of schizonts grown in the first cycle ex vivo prior to any erythrocyte invasion, expression levels of a selected panel of these genes vary among isolates, but mean levels are similar to those in the continuously cultured clinical isolates, indicating that the latter are useful for experimental studies requiring biological replication.

scholarly journals A Dual Infection/Competition Assay Shows a Correlation between Ex Vivo Human Immunodeficiency Virus Type 1 Fitness and Disease Progression

2000 ◽  
Vol 74 (19) ◽  
pp. 9222-9233 ◽  
Author(s):  
Miguel E. Quiñones-Mateu ◽  
Sarah C. Ball ◽  
Andre J. Marozsan ◽  
Vincent S. Torre ◽  
Jamie L. Albright ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Ex Vivo ◽  
Relative Fitness ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT This study was designed to examine the impact of human immunodeficiency virus type 1 (HIV-1) fitness on disease progression through the use of a dual competition/heteroduplex tracking assay (HTA). Despite numerous studies on the impact of HIV-1 diversity and HIV-specific immune response on disease progression, we still do not have a firm understanding of the long-term pathogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and CD4-positive T-helper cell responses directed toward HIV-infected cells appear to curb HIV pathogenesis. However, the rate at which the virus infects the CD4+ T-cell population and possibly destroys the HIV-specific immune response may also alter the rate of disease progression. For HIV-1 fitness studies, we established conditions for dual HIV-1 infections of peripheral blood mononuclear cells (PBMC) and a sensitive HTA to measure relative virus production. A pairwise comparison was then performed to estimate the relative fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syncytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (two NSI/R5 and two SI/X4) with moderate ex vivo fitness were then selected as controls and competed against primary HIV-1 isolates from an HIV-infected Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompeted by control strains and were significantly less fit than HIV-1 isolates from patients with accelerated progression to AIDS (PRO). In addition, NSI/R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that not all SI/X4 HIV-1 isolates replicate more efficiently than all NSI/R5 isolates. Finally, there were strong, independent correlations between viral load and the total relative fitness values of HIV-1 isolates from PRO (r = 0.84, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS plots suggest that HIV-1 fitness together with viral load may be a strong predictor for the rate of disease progression.

scholarly journals An International Commentary on Dysphagia and Dysphonia During the COVID-19 Pandemic

Dysphagia ◽  
2022 ◽  
Author(s):  
Anna Miles ◽  
Jackie McRae ◽  
Gemma Clunie ◽  
Patricia Gillivan-Murphy ◽  
Yoko Inamoto ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Well Being ◽  
Primary Data ◽  
International Expert ◽  
Travel Restrictions ◽  
The Impact ◽  
Health And Well Being

AbstractCOVID-19 has had an impact globally with millions infected, high mortality, significant economic ramifications, travel restrictions, national lockdowns, overloaded healthcare systems, effects on healthcare workers’ health and well-being, and large amounts of funding diverted into rapid vaccine development and implementation. Patients with COVID-19, especially those who become severely ill, have frequently developed dysphagia and dysphonia. Health professionals working in the field have needed to learn about this new disease while managing these patients with enhanced personal protective equipment. Emerging research suggests differences in the clinical symptoms and journey to recovery for patients with COVID-19 in comparison to other intensive care populations. New insights from outpatient clinics also suggest distinct presentations of dysphagia and dysphonia in people after COVID-19 who were not hospitalized or severely ill. This international expert panel provides commentary on the impact of the pandemic on speech pathologists and our current understanding of dysphagia and dysphonia in patients with COVID-19, from acute illness to long-term recovery. This narrative review provides a unique, comprehensive critical appraisal of published peer-reviewed primary data as well as emerging previously unpublished, original primary data from across the globe, including clinical symptoms, trajectory, and prognosis. We conclude with our international expert opinion on what we have learnt and where we need to go next as this pandemic continues across the globe.

Abstract 3133: Impact of Post-stroke Isolation on Stroke Outcome

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Venugopal R Venna ◽  
Yan Xu ◽  
Jun Li ◽  
Fudong Liu ◽  
Louise D McCullough
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Forced Swim Test ◽  
Statistical Significance ◽  
Experimental Studies ◽  
Stroke Recovery ◽  
Stroke Outcome ◽  
Post Stroke ◽  
The Impact

Background: Psychosocial factors are increasingly accepted as critical factors in post-stroke recovery, mortality and morbidity. Although, emerging data from clinical and population based studies support the role of social support in improved functional recovery and reducing the risk of mortality, to date no experimental studies have investigated such effects in post-stroke animal models. The aim of this study is to investigate for the impact of post stroke housing and the effects of long-term social isolation and pair housing with either a healthy or a stroked partner, and explored for the mechanisms. Methods: Male mice (20-25g; C57BL/6N, Charles River Labs), all initially pair housed, were subjected to right middle cerebral artery occlusion (MCAO - 60min) and then randomly assigned to a specific housing condition - isolated, paired with a stroke partner or paired with a healthy partner. Infarct size was quantified with TTC 72h after stroke (n=8/grp). We then investigated the effects of housing on long-term functional recovery using corner test, cylinder test, forced swim test (FST) and tail suspension test (TST). We further explored the mechanisms underlying the improved behavioral recovery by injecting BrDU 150mg/kg/day i.p. for 5 days starting from day 3 post-stroke (n=8/grp), and assessing changes in BDNF levels by western-blot analysis (n=4/grp). Data were expressed as mean±sem. Two-way ANOVA was performed and P value < .05 was set for statistical significance. Results: Post-stroke housing conditions can significantly impact infarct size; we observed that mice isolated after stroke had increased infarct volume compared to pair housed mice in all three brain regions (Cortex: 63.2±2.5 vs 40.0±6.2; p<0.01); (Striatum: 86.6±2.2 vs 67.7±2.9; p<0.01); (Total: 60.9±1.3 vs 32.6±4.3; p<0.01). Although post-stroke housing with healthy vs a stroked partner did not influenced infarct size (p>0.05), animals pair housed with healthy partner showed a significantly improved functional recovery by as early as day 15 in the cylinder and corner tests (p<0.05). Increased mobility was observed in FST and TST in PH mice compared to SI mice at day 90 (p<0.05). Consistently, housing with a healthy partner increased BrDU positive cells (p<0.05) and enhanced BDNF expression compared to other cohorts (SI 1±0.1; PH with stroke partner 1.9±0.2; PH with healthy partner 2.6±0.1; n=4/grp), no changes were seen in sham mice. Conclusions: Post-stroke housing has an important impact on stroke outcome; isolation has a detrimental effect on infarct size compared to pair housed cohorts. Interestingly, independent of infarct size, housing with a healthy partner hastened recovery compared to those stroke mice housed with partner that had also been subjected to stroke. Molecular analysis indicates the involvement of BDNF and neurogenesis may be important regulators of post-stroke housing induced functional recovery.

The impact of corporate social responsibility (CSR) priming on consumers’ consumption and lifestyle choices with intertemporal tradeoffs

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Hajar Fatemi ◽  
Laurette Dube
Keyword(s):  
Corporate Social Responsibility ◽  
Social Responsibility ◽  
Experimental Studies ◽  
Unhealthy Food ◽  
Content Type ◽  
Trade Offs ◽  
Lifestyle Choices ◽  
Corporate Social ◽  
The Impact

Purpose This paper aims to study the unexplored possibility that priming firms’ corporate social responsibility (CSR) activity in consumers’ minds may impact consumers’ preference for non-firm related consumption and lifestyle choice options with intertemporal trade-offs. Design/methodology/approach Across four experimental studies, the authors looked at the impact of CSR priming on the preference of participants for later larger versus sooner smaller money (Study 1), saving versus spending (Study 2) and healthy versus unhealthy food choices (Studies 3 and 4). These choice options were not related to the focal firm that practiced CSR. The authors measured the changes in participants’ consideration of future consequences (CFC) as a potential mediator for the results. Findings The participants in the CSR condition showed a higher CFC and a higher preference for the options with long-term benefits and immediate costs over the ones with long-term costs and immediate benefits, i.e. later larger over sooner smaller money, saving over spending and healthy over unhealthy food. The authors documented a mediation role for CFC. Research limitations/implications All the participants in the studies were from the USA. Looking at the cultural differences can enrich the understanding of the impact of CSR on preference for the options with intertemporal trade-offs. Furthermore, this paper builds its theoretical justification based on the assumption of individuals’ acceptance of CSR activities. Nevertheless, consumers may have skepticism about these activities. Future studies may investigate the effect of CSR skepticism of individuals on the proposed effects. Additionally, investigating the moderating roles of individuals’ characteristics like their prosocial concern or their knowledge about choice options might be an avenue for future research. Practical implications The findings highlight the benefits of CSR priming on consumers’ welfare and normative behavior. Firms may use the findings to understand and manage the impact of other firms’ CSR communications on the evaluation of their own products. Originality/value This research is the first to highlight the impact of CSR priming on consumers’ non-firm-related consumption and lifestyle choices with intertemporal trade-offs. The results showed the positive effect of priming firms’ CSR activities on consumers’ CFC and the mediating role of CFC.

Impact of long-term experimental water level drawdown on vegetation and carbon gas dynamics of boreal mire ecosystems

2020 ◽  
Author(s):  
Eeva-Stiina Tuittila ◽  
Aino Korrensalo ◽  
Anna Laine ◽  
Nicola Kokkonen ◽  
Lauri Mehtätalo ◽  
...  
Keyword(s):  
Water Level ◽  
Gas Dynamics ◽  
Experimental Studies ◽  
Net Ecosystem Exchange ◽  
Woody Species ◽  
Long Term Results ◽  
Moss Species ◽  
Poor Fen ◽  
The Impact

&lt;p&gt;Recent paleoecological studies have demonstrated an ongoing drying trend in temperate and boreal peatlands in Europe and in Canada. This drying is likely to alter vegetation and carbon gas exchange with atmosphere. However, to revel the expected change in carbon gas dynamics associated with decrease in water level experimental studies and long-term monitoring are needed. In here we present results from long term experiment in Finland where the impact of water level drawdown (WLD) of ~10 cm on three different peatland sites, two fens and a bog, has been studied since year 2000.&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;Response to WLD differed between the three ecosystem types. In the nutrient rich fen WLD initiated rapid directional succession from sedge dominated system to the dominance of woody species. In the poor fen changes were less drastic: Initially WLD benefitted dwarf scrubs already present at the site, later they were overtaken by pines.&amp;#160; Sedges as a group hold their position but Carex species were replaced by Eriophorum. Similarly to sedges, in the moss layer proportions of different Sphagnum moss species changed. Bog vegetation was more stable than fen vegetation.&lt;/p&gt;&lt;p&gt;&amp;#160;&lt;/p&gt;&lt;p&gt;In all the ecosystems methane emissions decreased directly after WLD. In contrast, the response of CO2 dynamics was more complex. While long term net ecosystem exchange decreased to lower level than in controls in all studied ecosystems, the response of photosynthesis and respiration differed between the three ecosystems and between short term and long term. Results show how the response of peatlands to climate change is diverse and emphasize the need to understand what factors regulate the stability and resilience of peatland functioning.&lt;/p&gt;

scholarly journals Maintaining Plasmodium falciparum gametocyte infectivity during blood collection and transport for mosquito feeding assays in the field

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Harouna M. Soumare ◽  
Wamdaogo Moussa Guelbeogo ◽  
Marga van de Vegte-Bolmer ◽  
Geert-Jan van Gemert ◽  
Zongo Soumanaba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Water Temperature ◽  
The Gambia ◽  
Short Term ◽  
Infected Blood ◽  
Membrane Feeding ◽  
Thermos Flask ◽  
The Impact

Abstract Background Mosquito feeding assays using venous blood are commonly used for evaluating the transmission potential of malaria infected individuals. To improve the accuracy of these assays, care must be taken to prevent premature activation or inactivation of gametocytes before they are fed to mosquitoes. This can be challenging in the field where infected individuals and insectary facilities are sometimes very far apart. In this study, a simple, reliable, field applicable method is presented for storage and transport of gametocyte infected blood using a thermos flask. Methods The optimal storage conditions for maintaining the transmissibility of gametocytes were determined initially using cultured Plasmodium falciparum gametocytes in standard membrane feeding assays (SMFAs). The impact of both the internal thermos water temperature (35.5 to 37.8 °C), and the external environmental temperature (room temperature to 42 °C) during long-term (4 h) storage, and the impact of short-term (15 min) temperature changes (room temp to 40 °C) during membrane feeding assays was assessed. The optimal conditions were then evaluated in direct membrane feeding assays (DMFAs) in Burkina Faso and The Gambia where blood from naturally-infected gametocyte carriers was offered to mosquitoes immediately and after storage in thermos flasks. Results Using cultured gametocytes in SMFAs it was determined that an internal thermos water temperature of 35.5 °C and storage of the thermos flask between RT (~ 21.3 °C) and 32 °C was optimal for maintaining transmissibility of gametocytes for 4 h. Short-term storage of the gametocyte infected blood for 15 min at temperatures up to 40 °C (range: RT, 30 °C, 38 °C and 40 °C) did not negatively affect gametocyte infectivity. Using samples from natural gametocyte carriers (47 from Burkina Faso and 16 from The Gambia), the prevalence of infected mosquitoes and the intensity of oocyst infection was maintained when gametocyte infected blood was stored in a thermos flask in water at 35.5 °C for up to 4 h. Conclusions This study determines the optimal long-term (4 h) storage temperature for gametocyte infected blood and the external environment temperature range within which gametocyte infectivity is unaffected. This will improve the accuracy, reproducibility, and utility of DMFAs in the field, and permit reliable comparative assessments of malaria transmission epidemiology in different settings.

scholarly journals Analysis of the role of TpUB05 antigen from Theileria parva in immune responses to malaria in humans compared to its homologue in Plasmodium falciparum; UB05 antigen

2019 ◽  
Author(s):  
Jerome Nyhalah Dinga ◽  
Stanley Dobgima Gamua ◽  
Dieudonné Lemuh Njimoh ◽  
Francis N. G. Chuma ◽  
Apollinaire Djikeng ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Theileria Parva ◽  
Endemic Region ◽  
Experimental Conditions ◽  
Potential Marker ◽  
As Species

Abstract Despite the amount of resources deployed and technological advancements in Molecular Biology, vaccinology, immunology, genetics, and biotechnology, there is still no effective vaccines against malaria. Immunity to either malaria or East Coast fever is usually seen as species- and/or strain-specific. But there is growing body of evidence suggesting the possibility of the existence of cross strain, cross species and cross genus immune responses in apicomplexans. The principle of gene conservations indicates that homologues play similar role in closely related organisms. UB05 antigen (XP_001347656.2) from Plasmodium falciparum is part of chimeric UB05-09 antigen; a potential vaccine candidate has been demonstrated to be a marker of protective immunity in malaria. The homologue of UB05 in Theileria parva is TpUB05 (XP_763711.1) which was also tested and shown to be a potential marker of protective immunity in ECF as well. In a bid to identify potent markers of protective immunity to aid malaria vaccine development, TpUB05 was tested in malaria caused by Plasmodium falciparum . UB05 antigen was tested in malaria using ELISpot, ELISA, and Growth Inhibition assays with samples from a malaria endemic region, and published. During these same experiments, TpUB05 antigen was tested alongside UB05, in separate wells but on the same plates and exposed to the same experimental conditions and the result presented here. Here we compare the performance of TpUB05 to that of UB05 in terms of the type and magnitude of immune responses provoked in malaria. It was observed that TpUB05 provoked stronger immune responses in malaria compared to UB05 antigen ex-vivo . This suggests that TpUB05 from Theileria parva is a better marker of protective immunity in malaria compared to its homologue UB05 from Plasmodium falciparum .

scholarly journals Maintaining Plasmodium Falciparum Gametocyte Infectivity During Blood Collection and Transport for Mosquito Feeding Assays in the Field

2021 ◽  
Author(s):  
Harouna M. Soumare ◽  
Wamdaogo Moussa Guelbeogo ◽  
Marga van-de Vegte-Bolmer ◽  
Geert-Jan van Gemert ◽  
Zongo Soumanaba Soumanaba ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Water Temperature ◽  
The Gambia ◽  
Short Term ◽  
Infected Blood ◽  
Membrane Feeding ◽  
Thermos Flask ◽  
The Impact

Abstract BackgroundMosquito feeding assays using venous blood are commonly used for evaluating the transmission potential of malaria infected individuals. To improve the accuracy of these assays, care must be taken to prevent premature activation or inactivation of gametocytes before they are fed to mosquitoes. This can be challenging in the field where infected individuals and insectary facilities are sometimes very far apart. In this study, a simple, reliable, field applicable method is presented for storage and transport of gametocyte infected blood using a thermos flask. MethodsThe optimal storage conditions for maintaining the transmissibility of gametocytes were determined initially using cultured Plasmodium falciparum gametocytes in standard membrane feeding assays (SMFAs). The impact of both the internal thermos water temperature (35.5 – 37.8°C), and the external environmental temperature (room temp – 42°C) during long-term (4hr) storage, and the impact of short-term temperature changes (room temp – 40°C) during membrane feeding assays was assessed. The optimal conditions were then evaluated in direct membrane feeding assays (DMFAs) in Burkina Faso and The Gambia where blood from naturally infected gametocyte carriers was offered to mosquitoes immediately and after storage in thermos flasks. ResultsUsing cultured gametocytes in SMFAs it was determined that an internal thermos water temperature of 35.5°C and storage of the thermos flask between RT (~21.3°C) and 32°C was optimal for maintaining transmissibility of gametocytes for 4 hours. Short-term storage of the gametocyte infected blood at temperatures up to 38°C (range: RT, 30°C and 38°C) did not have a negative effect on gametocyte infectivity. Using samples from natural gametocyte carriers (47 from Burkina Faso and 16 from The Gambia), the prevalence of infected mosquitoes and the intensity of oocyst infection was maintained when gametocyte infected blood was stored in a thermos flask in water at 35.5°C for up to 4 hours.ConclusionsThis study determines the optimal long-term (4 hours) storage temperature for gametocyte infected blood and the external environment temperature range within which gametocyte infectivity is unaffected. This will improve the accuracy, reproducibility, and utility of DMFAs in the field, and permit reliable comparative assessments of malaria transmission epidemiology in different settings.

scholarly journals Vision of the role of long-term social stress in the formation of "diseases of civilization". mechanisms of adaptation to stressor situations and factors of its failure

2021 ◽  
Vol 11 (10) ◽  
pp. 325-331
Author(s):  
O. Hancheva ◽  
K. Romanova
Keyword(s):  
Social Stress ◽  
Experimental Studies ◽  
Human Diseases ◽  
Stress Reactions ◽  
Sources Of Information ◽  
Negative Effects ◽  
Scientific Publications ◽  
The Impact

Today, the issue of studying the mechanisms of the impact of social stress on public health and its role in the formation of key human diseases is relevant and necessary. A large number of works, both clinical observations and experimental studies, are devoted to this problem. However, despite the high interest in this problem, there are still "white spots". Therefore, the purpose of our study was to analyze modern sources of information that highlight current issues of long-term social stress and its role in the formation of "diseases of civilization." Matherials and methods: analysis of scientific publications from the following databases: Google Scholar, Web of Science, Pub Med, by keywords: rats, social stress, diseases of civilization, neuroendocrine regulation, hypothalamus, supraoptic nucleus, paravetricular nucleus. Conclusions: Thus, the analysis of resources shows the undoubted role of stress in the formation of human diseases. Many articles are devoted to the description and analysis of the negative effects of environmental factors and peculiarities of living conditions on human health. Most researchers agree on the key role of the hypothalamus in regulating the body's stress response and the presence of morphofunctional changes associated with stress. It is important to note that scientists have paid much attention to the study of individual models of stress, namely pain, immobilization and hypoxic over the past 20 years. Unfortunately, there are few facts concerning the analysis of the influence of long-term negative social factors that do not cause stereotyped reactions, but form latent changes that are inherent in classical stress reactions.

scholarly journals Impact of climate extremes on wildlife plant flowering over Germany

2015 ◽  
Vol 12 (22) ◽  
pp. 18389-18423 ◽  
Author(s):  
J. F. Siegmund ◽  
M. Wiedermann ◽  
J. F. Donges ◽  
R. V. Donner
Keyword(s):  
Experimental Studies ◽  
Climate Extremes ◽  
Systematic Investigation ◽  
Early Spring ◽  
Statistical Tool ◽  
Temperature And Precipitation ◽  
The Earth ◽  
Spring Temperatures ◽  
The Impact

Abstract. Ongoing climate change is known to cause an increase in the frequency and amplitude of local temperature and precipitation extremes in many regions of the Earth. While gradual changes in the climatological conditions are known to strongly influence plant flowering dates, the question arises if and how extremes specifically impact the timing of this important phenological phase. In this study, we systematically quantify simultaneities between meteorological extremes and the timing of flowering of four shrub species across Germany by means of event coincidence analysis, a novel statistical tool that allows assessing whether or not two types of events exhibit similar sequences of occurrences. Our systematic investigation supports previous findings of experimental studies by highlighting the impact of early spring temperatures on the flowering of wildlife plants. In addition, we find statistically significant indications for some long-term relations reaching back to the previous year.

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